Antibiotic resistance is a big danger for modern medicine. Bacteria change fast, and medicines that used to work can stop working. This makes simple infections harder to treat and raises the risk of surgery, cancer care, and other procedures.
Scientists around the world are looking for ways to stay ahead of these fast‑changing germs. One hopeful idea is not to create a brand‑new drug, but to help old drugs work again. These helpers are called antibiotic adjuvants. They don’t kill bacteria themselves; they make existing antibiotics stronger.
Fast Chemistry to Build New Molecules
Professor John Moses and his team at Cold Spring Harbor Laboratory have spent years improving the chemistry that creates new drug‑like molecules. They use a method they invented called diversity‑oriented clicking (DOC). With DOC they built a library of more than 150 different compounds. Some of these molecules have already helped research on antibiotic resistance and cancer.
Working together with researchers at Scripps, the library helped bring back the power of vancomycin. Vancomycin is a strong antibiotic used for serious infections, including those caused by MRSA and Clostridium difficile. Both germs can become “superbugs” that ignore vancomycin and spread in hospitals and communities.
Making Vancomycin Effective Again
In the new study, Moses’s lab joined forces with Professor Howard Hang’s group at Scripps. They focused on a bacterial enzyme named secreted antigen A (SagA). By blocking SagA with a small molecule called pghi‑4, they stopped the enzyme from protecting the bacteria.
When drug‑resistant Enterococcus faecium was given both vancomycin and pghi‑4, the antibiotic could kill the germs once more.
Professor Moses says the breakthrough started from basic chemistry, not from hunting a new antibiotic. “We were improving reactions, and that led us to the first blocker of an enzyme that causes resistance,” he explained.
A Bigger Plan Against Superbugs
The team now shares their molecular library with other scientists. They hope similar chemistry tricks can help treat more resistant infections, such as tough forms of tuberculosis.
“Our chemistry is designed to speed up drug discovery,” Moses added. “By using reliable, smart reactions, we can build useful molecules faster.”
As antibiotic resistance spreads worldwide, this work shows that new treatments can come from rethinking old drugs. The next breakthrough may start with a tiny helper molecule that makes an existing antibiotic work again.
Funding
Supported by the National Institutes of Health, National Cancer Institute, Australian Research Council, New York State Biodefense Commercialization Fund, F.M. Kirby Foundation, and Starr Foundation.